Method and apparatus for measuring physico-chemical properties using a nuclear magnetic resonance spectrometer

ABSTRACT

Methods for measuring physico-chemical properties using a nuclear magnetic resonance spectrometer are disclosed, including methods to determine an initial amount of a substance, usually a liquid, contained inside a porous material and an initial amount of the substance, usually a liquid, present outside the porous material, methods to measure the release kinetics of a substance, such as a liquid, from a porous material, and methods for performing chemical reactions and other physico-chemical operations in situ inside a nuclear magnetic resonance probe after a sample is loaded into a nuclear magnetic resonance spectrometer. The apparatuses for performing these methods are also disclosed.

FIELD OF THE INVENTION

This invention relates to measuring physico-chemical properties ofmaterials using nuclear magnetic resonance spectroscopy (“NMR”). Inparticular, some aspects of the invention relate to a method ofmeasuring and interpreting a sample's NMR transverse relaxation and anapparatus performing such a method. The apparatus and method may includecomponents for performing chemical reactions and transport phenomena insitu inside a NMR probe, and therefore other aspects of the inventionrelate to an apparatus and method for performing in situ reactions forNMR spectroscopy.

BACKGROUND

NMR spectroscopy is known as one of the most important diagnostic toolsavailable to scientists and engineers across a wide range of fields.Therefore, this disclosure assumes familiarity with the primary aspectsof NMR spectroscopy and experiments, and will only focus on the aspectsmost relevant to the applications described herein rather than providingan exhaustive summary. To the extent further explanation may be helpful,review of J. Keeler, Understanding NMR Spectroscopy, Wiley, 2006; B.Cowan, Nuclear Magnetic Resonance and Relaxation, Cambridge UniversityPress, 1997; J. Kowalewski and L. Maier, Nuclear Spin Relaxation inLiquids, Taylor & Francis, 2006; or similar references can helpelucidate the foundational principles of the field.

Numerous atoms with odd atomic numbers and/or odd atomic mass numberssuch as Hydrogen have nonzero nuclear spin and therefore possess anuclear magnetic moment. An atom such as Hydrogen with a spin quantumnumber of I=½ has two possible nuclear spin states when placed in amagnetic field as its nuclear magnetic moment orients relative to thefield. In one spin state the nuclear magnetic moment orients parallel tothe direction of the applied magnetic field while the other orientsdirectly against the direction of the applied field. Under Boltzmann'slaw and in thermal equilibrium, there is a slight preference for thatalignment that has a lower energy, meaning for a sample comprising manyHydrogen nuclei (or nuclei with similar spin properties), the overallspin population of the sample favors this state. Therefore, the overallmagnetic moment of a sample is typically characterized as showing thesample has a net nuclear magnetization along the direction of thez-axis, where this axis is defined by the direction of the appliedmagnetic field.

When the sample is irradiated with a radiofrequency (“RF”) pulse,generating a second magnetic field, one may probe the properties of thesample by reorienting the overall nuclear magnetization vector of thesample and manipulating the relative populations of the overall spins.Often, a RF pulse will be applied to a sample such that itsmagnetization is moved from the z-axis into a coherent vector in the x-y(transverse) plane. Once the RF pulse is finished, however, the creatednuclear magnetization in the transverse plane decays to zero in aprocess called transverse relaxation while the magnetization along thez-axis relaxes back to its value attained in thermal equilibrium in aprocess called longitudinal relaxation. The measured decay of signal inthe transverse plane provides the transverse, relaxation time typicallydenoted as T₂.

NMR experiments may be performed on a wide variety of molecules.Transverse relaxation times for molecules, however, are sensitive tomolecular motions. Therefore, experiments directed to samples where someamount of the sample material has a greater degree of molecular motioncompared to some other amount of the same material that is constrainedor contained in some way, such as within a porous material, will observedifferences in the transverse relaxation times between the constrainedand unconstrained material. In these systems, quantifying the relativeamounts of free, out-of-pore material and constrained in-pore materialis far from straightforward. This is especially true when the materialis a liquid due to factors including the distribution of liquidproperties, the pore size variance and distribution, and differences inthe size of liquid droplets. Therefore, typical multiexpoential fits ofthe experimental transverse relaxation decays are not suitable as theyprovide strongly model dependent answers.

Certain types of NMR experiments may also relate to measuring thekinetics of a system, such as a chemical reaction or a chemicaltransport phenomenon. Due to the inherent time (in the order of 10seconds or longer) needed to load an NMR sample into the spectrometer,however, conventional techniques preclude measuring the immediatekinetics or characteristics of a system or transformation after thesample is prepared, as the chemical reaction or transformation begins toproceed before the sample is loaded in the spectrometer.

To alleviate these inefficiencies, it may be desirable to utilize amethod and apparatus that accurately allows the differentiation ofconstrained and unconstrained materials. It may also be desirable toutilize a method and apparatus that allows initiation of a chemicalreaction or other transformation only after the sample is loaded intothe NMR spectrometer and ready for measurement.

The invention provides NMR methods and apparatuses that, amongst otherfeatures and advantages, address these objectives. Certain embodimentsof the invention provide a method and apparatus for determining aninitial amount of a substance such as a liquid contained inside a porousmaterial and an initial amount of the substance such as a liquid presentoutside the porous material using a nuclear magnetic resonancespectrometer. Certain other embodiments provide a method for measuringthe release kinetics of a substance such as a liquid from a porousmaterial using a nuclear magnetic resonance spectrometer. Still otherembodiments provide an apparatus and method for performing chemicalreactions or other transformations in situ inside a nuclear magneticresonance probe after a sample is loaded into a nuclear magneticresonance spectrometer. These and other objects, features and advantagesof the invention or of certain embodiments of the invention will beapparent to those skilled in the art from the following disclosure anddescription of exemplary embodiments.

SUMMARY

In accordance with one aspect of the invention, a method for measuringphysico-chemical properties of a sample, such as the sample's releasekinetics properties, using a nuclear magnetic resonance spectrometer isdisclosed, the method comprising placing the sample inside a nuclearmagnetic resonance probe, wherein the sample comprises a porous materialand a substance such as a liquid that is at least partially containedinside the porous material, applying a first radiofrequency pulse orpulse sequence to the sample, measuring a first transverse relaxationdecay of the sample and performing an inverse Laplace transformation onthe first measured transverse relaxation decay to determine an initialamount of the substance such as the liquid contained inside the porousmaterial and an initial amount of the substance such as the liquidpresent outside the porous material.

In certain of these embodiments, the sample comprises a contactingsolution and the method further comprises exposing the porous materialand the substance such as the liquid to the contacting solution, waitinga predetermined time period after the first measurement of the sample'stransverse relaxation, applying at least one subsequent radiofrequencypulse or pulse sequence to the sample, measuring at least one subsequenttransverse relaxation decay of the sample, performing an inverse Laplacetransformation on the at least one subsequent transverse relaxationdecay to determine at least one subsequent amount of the substance suchas the liquid contained inside the porous material and at least onesubsequent amount of the substance such as the liquid present outsidethe porous material and comparing the initial amounts of the substancesuch as the liquid inside and outside the porous material to the atleast one subsequent amounts of the substance such as the liquid insideand outside the porous material.

In certain embodiments, the pulse or pulse sequence is aCarr-Purcell-Meiboom-Gill (CPMG) radiofrequency pulse sequence. Inothers, the contacting solution comprises water, a buffer, an organicsolvent, an inorganic solvent, a model saliva solution, a model bloodsolution, a model gastric acid solution, or a combination thereof. Inyet other embodiments, the contacting solution is substantially orentirely Deuterated. In yet other embodiments, the substance of interestcontains a unique NMR nucleus such as but not exclusively ³¹P, ¹⁹F, ²³Nathat is not present in the contacting solution. In all theseembodiments, the NMR signal that is unique to the substance of interestis detected while the NMR signal of the contacting solution is notdetected, or is only detected in small amounts. In still otherembodiments, the substance such as the liquid comprises an edibleorganic compound, an edible oil, a flavorant, a sweetener, apharmaceutical compound, a medicament, an ink, or a combination thereof.

In some embodiments, the porous material and the substance such as aliquid are exposed to the contacting solution in situ inside the probeafter the probe is loaded into the nuclear magnetic resonancespectrometer such that the probe is ready for measurement of thesample's transverse relaxation. In other embodiments, the porousmaterial and the substance such as a liquid are stored inside a firstcontainer, the contacting solution is stored inside a second container,the first container is contained inside the second container andseparates the porous material and the substance such as a liquid fromthe contacting solution, and the method further comprises exposing theporous material and the substance such as a liquid to the contactingsolution by removing the first container, forcing the porous materialand the substance such as a liquid out of the first container, or acombination thereof. In certain embodiments, the method furthercomprises applying an electric current to a conductor material toproduce a Lorentz force, where the Lorentz force acts upon the conductormaterial such that the conductor material initiates or performs theremoving of the first container, the forcing of the porous material andthe substance such as a liquid, or a combination thereof. In otherembodiments the conductor material is a solenoid coil and the electriccurrent produces a Lorentzian torque that causes the solenoid coil torotate. In still other embodiments, the porous material is an ediblegrain or particle, while in others it specifically comprises Silicondioxide particles.

In accordance with another aspect of the invention, an apparatus formeasuring physico-chemical properties, such as the diffusioncharacteristics of a sample using nuclear magnetic resonance isdisclosed, the apparatus comprising a nuclear magnetic resonance probesuitable for containing a sample, where the sample comprises a porousmaterial and a substance such as a liquid that is at least partiallycontained inside the porous material, and one or more non-transitorycomputer readable media storing computer readable instructions that,when executed by a computer processor, cause the apparatus to performapplying a first radiofrequency pulse or pulse sequence to the sample,measuring a first transverse relaxation decay of the sample andperforming an inverse Laplace transformation using the computerprocessor on the first transverse relaxation decay to determine aninitial amount of the substance such as a liquid contained inside theporous material and an initial amount of the substance such as a liquidoutside the porous material.

In some embodiments, the sample further comprises a contacting solutionand the computer readable instructions, when executed, cause theapparatus to perform exposing the porous material and the substance suchas a liquid to the contacting solution, waiting a predetermined timeperiod after the measurement of the sample's first transverserelaxation, applying at least one subsequent radiofrequency pulse orpulse sequence to the sample, measuring at least one subsequenttransverse relaxation decay of the sample. performing an inverse Laplacetransformation on the at least one subsequent transverse relaxationdecay to determine at least one subsequent amount of the substance suchas a liquid contained inside the porous material and at least onesubsequent amount of the substance such as a liquid outside the porousmaterial and comparing the initial amounts of substance such as a liquidinside and outside the porous material to the at least one subsequentamounts of substance such as a liquid inside and outside the porousmaterial. In yet other embodiments the porous material and the substancesuch as a liquid are stored inside a first container, a contactingsolution is stored inside a second container, the first container iscontained inside the second container and separates the porous materialand the substance such as a liquid from the contacting solution and thefirst container is connected to an exposure mechanism. In otherembodiments the exposure mechanism comprises an electrical source and aconductor material electrically connected to the electrical source,where the conductor material is directly or indirectly connected to thefirst container.

In accordance with another aspect of the invention, a method formeasuring the release kinetics of a substance such as a liquid from aporous material using a nuclear magnetic resonance spectrometer isdisclosed, the method comprising placing a sample inside a nuclearmagnetic resonance probe, wherein the sample comprises a porousmaterial, a substance such as a liquid that is at least partiallycontained inside the porous material, and a contacting solution, whereinthe contacting solution is separated from the porous material and thesubstance such as a liquid. The method in accordance with the aspect ofthis invention further comprises exposing the porous material and thesubstance such as a liquid to the solution, applying a firstradiofrequency pulse or pulse sequence to the sample and beginning ameasurement of a first transverse relaxation decay of the sample,waiting a predetermined time period after the measurement of thesample's first transverse relaxation, applying at least one subsequentradiofrequency pulse or pulse sequence to the sample, measuring at leastone subsequent transverse relaxation decay of the sample, performing aninverse Laplace transformation on the first measured transverserelaxation decay to determine an initial amount of the substance such asa liquid contained inside the porous material and an initial amount ofthe substance such as a liquid present in the contacting solutionoutside the porous material, performing an inverse Laplacetransformation on the at least one subsequent transverse relaxationdecay to determine at least one subsequent amount of the substance suchas a liquid contained inside the porous material and at least onesubsequent amount of the substance such as a liquid in the containingsolution outside the porous material and comparing the initial amountsof substance such as a liquid inside the porous material and thecontacting solution to the at least one subsequent amounts of substancesuch as a liquid inside the porous material and the contacting solutionto determine the release kinetics of the substance such as a liquid intothe contacting solution without use of a multi-exponential fit.

In certain embodiments, the porous material is an edible grain orparticle. In yet others, the contacting solution comprises water, abuffer, an organic solvent, an inorganic solvent, a model salivasolution, a model blood solution, a model gastric acid solution, or acombination thereof. In still others, the substance such as a liquidcomprises an edible organic compound, an edible oil, a flavorant, asweetener, a pharmaceutical compound, an ink, or a combination thereof.

In accordance with another aspect of the invention, an apparatus forperforming chemical reactions or other physico-chemical transformationsin situ inside a nuclear magnetic resonance probe is disclosed, theapparatus comprising a sample container, a separator that separates atleast a first sample component of a sample from at least a second samplecomponent of the sample inside the sample container, an exposuremechanism connected to the separator that can expose at least the firstsample component to at least the second sample component inside thesample container, wherein the exposure mechanism can be selectivelyactivated to expose at least the first sample component to at least thesecond sample component inside the sample container at any time afterthe components are loaded, including when the sample is loaded in thenuclear magnetic resonance probe such that it is ready for theapplication of a radiofrequency pulse or pulse sequence by the nuclearmagnetic resonance probe, and wherein the sample components, when thesample container is loaded into the nuclear magnetic resonancespectrometer, are positioned within a sample space encircled by a probecoil of the nuclear magnetic resonance probe.

In certain embodiments the exposure mechanism is configured to lift theseparator from the sample, force at least the first sample componentinto contact with the second sample component, or a combination thereofwhen activated. In others the exposure mechanism further comprises anelectrical source and a conductor material electrically connected to theelectrical source, where the conductor material is directly orindirectly connected to the separator. In yet others the conductormaterial is mounted such that it will move or rotate in a particular waydue to a Lorentz force when an electrical current is supplied by theelectrical source to the conductor material and the conductor materialis in the presence of a magnetic field. In certain other embodiments theconductor material is a solenoid coil and the electric current producesa Lorentzian torque that causes the solenoid coil to rotate. In stillothers the rotation of the solenoid coil lifts up the separator whilemechanically forcing at least the first sample component into contactwith at least the second sample component.

In other embodiments, the separator is a tube having a first diameter,the sample container is a tube having a second diameter, the seconddiameter being larger than the first diameter. In yet other embodiments,the separator is hermetically sealed to the bottom of the samplecontainer. In certain other embodiments, the exposure mechanism furthercomprises a shaft capable of moving at least the first sample componentalong a longitudinal axis of the apparatus such that it drives at leastthe first sample component into at least the second sample component. Inyet other embodiments, all components of the holder, separator, samplecontainer and exposure mechanism that are in contact with the sample orcome into close proximity to the sample are made of materials that aresubstantially or completely free of hydrogen.

In accordance with another aspect of the invention, a method forperforming chemical reactions or other physico-chemical transformationsin situ inside a nuclear magnetic resonance probe is disclosed, themethod comprising loading a sample into a sample container, wherein aseparator separates at least a first sample component of the sample fromat least a second sample component of the sample inside the samplecontainer, placing the sample into a nuclear magnetic resonancespectrometer, wherein the sample components, once the sample is placedinto the nuclear magnetic resonance spectrometer, are positioned withina sample space encircled by a probe coil of a nuclear magnetic resonanceprobe, and exposing at least the first sample component to at least thesecond sample component inside the sample container when the sample isready for the application of a radiofrequency pulse or pulse sequence bya nuclear magnetic resonance probe.

In certain embodiments, the first sample component is exposed to atleast the second sample component by lifting the separator from thesample, forcing at least the first sample component into contact withthe second sample component, or a combination thereof. In otherembodiments, the method further comprises applying an electrical currentto a conductor material such that the conductor material moves orrotates in a particular way due to a Lorentz force. In yet otherembodiments, the conductor material is a solenoid coil and the electriccurrent produces a Lorentzian torque that causes the solenoid coil torotate. In still others, the rotation of the solenoid coil lifts up theseparator while mechanically forcing at least the first sample componentinto contact with at least the second sample component. In certainothers, the separator is a tube having a first diameter, the samplecontainer is a tube having a second diameter, the second diameter beinglarger than the first diameter. In yet other embodiments, the methodfurther comprises forcing at least the first sample component intocontact with at least the second sample component using a shaft movingalong a longitudinal axis of the apparatus.

In accordance with still another aspect of the invention, an apparatusfor performing chemical reactions or other physico-chemical operationsor transformations in situ inside a nuclear magnetic resonance probe isdisclosed, the apparatus comprising a sample container, a separator thatseparates at least a first sample component of a sample from at least asecond sample component of the sample inside the sample container,wherein at least one sample component comprises a solid material andwherein the sample components, when the sample container is loaded intothe nuclear magnetic resonance spectrometer, are positioned within asample space encircled by a probe coil of the nuclear magnetic resonanceprobe, and one or more non-transitory computer readable media storingcomputer readable instructions that, when executed by a computerprocessor, cause the apparatus to perform selectively activating theexposure mechanism to expose at least the first sample component to atleast the second sample component inside the sample container, applyinga first radiofrequency pulse or pulse sequence to the sample; andmeasuring the sample's magnetic resonance signals.

In certain embodiments, the exposure mechanism is configured to lift theseparator from the sample, force at least the first sample componentinto contact with the second sample component, or a combination thereofwhen activated. In yet others the exposure mechanism further comprisesan electrical source and a conductor material electrically connected tothe electrical source, where the conductor material is directly orindirectly connected to the separator and the conductor material ismounted such that it will move or rotate in a particular way due to aLorentz force when an electrical current is supplied by the electricalsource to the conductor material and the conductor material is in thepresence of a magnetic field.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the disclosure will now be described by way ofexample only and with reference to the accompanying drawings, in which:

FIG. 1 provides a representative transverse relaxation signal decaymeasured by a CPMG pulse sequence, for sunflower oil loaded in SP104particles.

FIG. 2 provides the result of an inverse Laplace transformation of thetransverse relaxation decay data of the embodiment from FIG. 1.

FIG. 3 provides the results of an inverse Laplace transformation of thetransverse relaxation decay data of medium chain triglyceride oil loadedinto SCTAB particles, where measurements were taken of the sample'sinitial transverse relaxation decay and then at a series ofrepresentative time periods after exposure to a mucin buffer solution.

FIG. 4 provides a kinetic plot of the data representing the amount ofmedium chain triglyceride oil within the pores at set times after theporous grains have been put into contact with the mucin buffer solutionfrom the embodiment shown in FIG. 3.

FIG. 5 provides an exemplary embodiment of an apparatus for performingchemical reactions or other physico-chemical transformations oroperations in situ inside an NMR probe.

FIG. 6 provides an exemplary plot showing the relative transverserelaxation proportions of a control sample and a sample with additionalout-of-pore liquid.

FIG. 7 provides an exemplary plot showing the relative transverserelaxation proportions of a control sample and a sample with additionalin-pore liquid.

FIG. 8 provides plots showing the release kinetics data of variousliquids from SP104 porous material.

FIG. 9 provides plots showing the release kinetics data of variousliquids from SCTAB porous material.

FIG. 10 provides plots showing the release kinetics data of sunfloweroil from SP104 porous material for an initial sample and a re-driedsample prepared from the same material.

FIG. 11 provides a plot showing the relative release kinetics data ofmedium chain triglyceride from different porous materials.

FIG. 12 provides a block diagram of an exemplary computing device thatmay be used with certain aspects of this disclosure.

FIG. 13 provides an illustrative diagram of an exemplary embodiment of acomputer operated NMR measurement apparatus.

DETAILED DESCRIPTION OF EMBODIMENTS

The embodiments, apparatuses and methods described herein providemethods for determining an initial amount of a substance such as aliquid contained inside a porous material and an initial amount of thesubstance such as a liquid present outside the porous material,measuring the release kinetics of a substance such as a liquid from aporous material, for performing chemical reactions or otherphysico-chemical transformations or operations in situ inside a nuclearmagnetic resonance probe after a sample is loaded into a nuclearmagnetic resonance spectrometer, and the apparatuses for performingthese methods. These and other aspects, features and advantages of theinvention or of certain embodiments of the invention will be furtherunderstood by those skilled in the art from the following description ofexemplary embodiments. It is to be understood that other embodiments maybe utilized and structural and functional modifications may be made.

As noted above, relaxation times are sensitive to molecular motions. Inparticular, the transverse relaxation of a material is sensitive tomolecular motions in the millisecond to nanosecond time interval. Theserelatively slower motions can shorten the transverse relaxation time ofa material. In a porous material, interactions or collisions between aliquid and the wall of the porous material or basic geographicconfinement due to the pore size can slow molecular motions andtherefore lower the transverse relaxation time of the liquid due tothese processes. In addition, the magnetic field within a random porousmaterial is typically very inhomogeneous because the magneticsusceptibility, or magnetization of a material in response to an appliedmagnetic field, is different for the pore filling liquid and the porousmaterial matrix. This inhomogeneity also promotes transverse relaxationby destroying coherence in the transverse plane since different nucleiexperience different magnetic fields which, moreover, may fluctuate asmolecules diffuse within the porous network.

In certain embodiments of the invention, a method is provided todetermine an initial amount of a substance such as a liquid containedinside a porous material and an initial amount of the substance such asa liquid present outside of the porous material by measuring and takingadvantage of the differences in transverse relaxation times for thein-pore and out-of-pore material (liquid). In some of these embodiments,a contacting solution is also present in or associated with the sample,where the porous material and the substance such as a liquid may or maynot be in contact with the contacting solution at the time of initialmeasurement. In certain embodiments, the porous material and thesubstance such as a liquid are not in contact with the contactingsolution for one or more measurements and subsequently are in contactwith the contacting solution for one or more measurements. Thetransverse relaxation decay may be measured for any NMR active nuclei,including but not limited to ¹H, ²H, ¹³C, ¹⁹F, ²³Na, and ³¹P.

In some of these embodiments, the porous material and contactingsolution (if present) preferably are substantially or entirely free ofthe nuclear species being measured. For example, in some embodimentsmeasuring the ¹H signal of the substance such as a liquid, the porousmaterial and contacting solution (if present) are inorganic materials,Deuterated materials, or a combination thereof. In other examples, insome embodiments measuring ¹⁹F or ³¹P signal of the liquid, the porousmaterial and contacting solution (if present) are substantially orentirely free of ¹⁹F, or ³¹P, respectively. In certain otherembodiments, however, this is not necessary as the transverse relaxationof the relevant species in the solid porous material is very short andcan be directly differentiated from the liquid's transverse relaxationor does not interfere with measurement of the liquid's transverserelaxation. As a representative example, the ¹H transverse relaxationtime of rigid cellulose or other rigid polymers is often on the timescale of 10 to 20 microseconds and therefore can be easily separatedfrom the ¹H transverse relaxation decay of liquids. In certainembodiments of the invention, consequently, the porous material cancomprise the nuclear species of interest provided it does not interferewith the measurement of the sample's signal under experimentalconditions.

The porous material, the substance of interest such as a liquid and thecontacting solution may be a wide variety of materials. In someembodiments, the substance such as a liquid is constituted by a singlematerial, while in others the substance such as a liquid is a solvent,carrier fluid, or liquid media that contains at least one other solid,liquid, or gas material. In certain embodiments, the liquid comprises anedible organic compound, an edible oil, a flavorant, a sweetener, apharmaceutical compound, a medicament, an ink, or a combination thereof.In still other embodiments, the liquid comprises a medium chaintriglyceride, propylene glycol, glycerine, citrus or other naturalflavorants, or sunflower oil. The porous material can be organic orinorganic.

Additional flavorants that are suitable in certain embodiments of theinvention are described in more detail in U.S. patent application Ser.No. 12/723,100, entitled “Anti-Caking Agent for Flavored Products,”which is hereby incorporated by reference in its entirety. In some ofthese embodiments, the liquid comprises a dissolved or suspended solidor liquid flavorant that includes extracts, essential oils, essences,distillates, resins, balsams, juices, sugars, botanical extracts,flavor, fragrance, or flavoring constituents derived from a spice, fruitor fruit juice, vegetable or vegetable juice, edible yeast, herb, bark,bud, root, leaf or similar plant material, meat, seafood, poultry, eggs,dairy products, or fermentation products.

In certain embodiments, the substance such as a medicament comprisesvitamins, minerals, nutritional supplements, diuretics, antivirals,antibiotics, anti-inflammatories, antitussives, or a combinationthereof. In yet other embodiments, the substance such as edible oilscomprises olive oil, peanut oil, safflower oil, corn oil, sunflower oil,cottonseed oils, canola, flax seed oil, coconut oil, palm oil, fish oil,avocado oil, walnut oil, macadamia nut oil, sesame seed oil, grapeseedoil, soybean oil, almond oil, orange oil, lime oil, black pepper oil,nutmeg oil, basil oil, rosemary oil, clove oil, grapefruit oil, fenneloil, coriander oil, bergamot oil, cinnamon oil, lemon oil, peppermintoil, garlic oil, thyme oil, marjoram oil, lemongrass oil, ginger oil,cardamom oil, or a combination thereof.

In certain embodiments, the porous material comprises one of more solidmaterials to form a porous matrix. In some embodiments, the porousmaterial has substantially uniform pore diameters or pore sizes. Inother embodiments, the porous material comprises pores with varyingsizes or diameters, and in yet others the porous material comprisesrelatively defined proportions of pores with a first size or diameterand pores with at least one other size or diameter. Use of the inventionis not constrained by the nature of the porous material as long as thesubstance of interest within the pores exhibits transverse relaxationtimes significantly different from that outside the pores. In someembodiments, the pore sizes or diameters can take any value in between 1and 1000 nanometers, while in others they are substantially equal to orsmaller than 500 nanometers. In others the pore sizes or diameters aresubstantially equal to or smaller than 250, 100 or 50 nanometers. In yetother embodiments, the pore sizes or diameters are between approximately0.1 and 1 micrometers, 0.1 and 0.5 micrometers, and 0.5 and 1micrometers, while in others there are between approximately 5 and 20nanometers, 25 and 50 nanometers, and 50 and 100 nanometers.

In some embodiments, the porous material is a grain or particle. Inother embodiments, the porous material is edible. In some of theseembodiments, the porous material comprises Silicon dioxide, Magnesiumoxide, Calcium oxide, Titanium dioxide, Zinc oxide, or a combinationthereof. In still other embodiments, the porous material comprisesmesoporous silica particles such as SP104 (mesoporous silica particlesfrom a P104 pluronic template), SCTAB (mesoporous silica particles froma cetyl trimethylammonium bromide template), or a combination thereof.Certain other embodiments of the porous material are also described inU.S. patent application Ser. No. 12/723,100, referenced above andincorporated in its entirety by reference to this disclosure.

In still other embodiments, the porous material comprises an acrylate, aplastic, a polymer or a combination thereof. In yet other embodiments,the porous material comprises a hydrogel, a soluble polymer, abiodegradable polymer, a natural gum, or a combination thereof. Incertain other embodiments, the porous material comprises polyethylene,polyvinyl chloride, ethyl cellulose, acrylate polymers, polyhydroxyethylmethylacrylate, cross-linked polyvinyl alcohol, cross-linked polyvinylpyrrolidone, polyacrylamide, polyethylene glycol, polyvinyl alcohol,polyvinyl pyrrolidone, hydroxypropyl methyl cellulose, polylactic acid,polyglycolic acid, polycaprolactone, a polyanhydride, a polyorthoester,polyethylene vinyl acetate, polydimethyl siloxane, polyether urethane,polyvinyl chloride, cellulose acetate, ethyl cellulose, polycarbophil,sodium carboxymethyl cellulose, polyacrylic acid, tragacanth, methylcellulose, pectin, xanthan gum, guar gum, karaya gum, or a combinationthereof.

In some embodiments, the contacting solution comprises water, a buffer,an organic solvent, an inorganic solvent, a model saliva solution, amodel blood solution, a model gastric acid solution, or a combinationthereof. In certain of these embodiments, the contacting solution issubstantially or entirely Deuterated so as to not interfere with the ¹HNMR measurement. In some of these embodiments, the solution is “heavy”water where Deuterium has substantially or entirely replaced Hydrogen inthe water. In certain other embodiments, the solution comprisesDeuterated acetone, Deuterated methanol, Deuterated dimethyl sulfoxide,Deuterated chloroform, Carbon tetrachloride, or Carbon disulphide or acombination thereof. In various other embodiments, the contactingsolution comprises an inorganic material. In yet other embodiments, thebuffer is a mucin buffer, an electrolyte buffer, or a combinationthereof.

In some embodiments an RF pulse or pulse sequences are used to measurethe transverse relaxation decay of a sample loaded in the NMRspectrometer. In certain embodiments, a 90 pulse is used to orient thesample's magnetization into the transverse plane. In other embodiments,a pulse sequence is used to refocus the magnetization in the transverseplane. In certain embodiments, a Hahn spin echo sequence or relatedsequence is used. In still other embodiments, a Carr-Purcell pulsesequence, Carr-Purcell-Meiboom-Gill (“CPMG”) pulse sequence, or arelated pulse sequence is used. The CPMG sequence and other pulsesequences aid the accurate measurement of the transverse relaxationdecay by at least correcting for magnetic field inhomogeneities and/orpulse accuracy errors. Another advantage of the CPMG sequence or similarsequences, however, is that they are relatively quick, often on thescale of approximately 100 milliseconds, which permits good temporalresolution in kinetic experiments.

Certain aspects of the invention relate to determining the amount of asubstance, usually a liquid, inside and outside a porous material usingthe sample's transverse relaxation.

FIG. 1 provides an exemplary embodiment's transverse relaxation curve10. In this exemplary embodiment, a Bruker Avance 500 NMR spectrometermeasured a sample of sunflower oil (liquid) loaded into SP104 mesoporoussilica particles using a CPMG sequence having 250 microsecond pulsespacing. Here only the early part of the decay is shown to emphasize thefast initial decay of signal in the transverse plane after the pulsesequence. Transverse relaxation curve 10 clearly shows themulti-exponential behavior of the signal decay. The fast initial decayis attributed to the shorter transverse relaxation time of sunflower oilcontained in the pores of the SP104 for the reasons discussed above,while the longer tail is attributed to out-of-pore oil. As notedearlier, however, it is difficult to properly apportion the relativeamount of oil in each of these states and multi-exponential fits arestrongly model dependent. General multi-exponential behavior provides atransverse relaxation decay that can be written as:

${I(t)} = {\int_{T_{2}\min}^{T_{2}\max}{{{A\left( T_{2} \right)} \cdot {\exp \left( {- \frac{t}{T_{2}}} \right)}}{dT}_{2}}}$

where I(t) is the exponential decay (as in FIG. 1) and A(T₂) is theweighing factor for a particular T₂, e.g. the T₂ relaxation time for thein-pore or out-of-pore oil in this embodiment. The weighing factor isproportional to the fraction of molecules in a particular environmentcharacterized by a given T₂ value, e.g. the ratio of in-pore toout-of-pore oil in this embodiment. Formally, I(t) is the Laplacetransform of the weighing factor. Since determination of the weighingfactor is needed to define the relative proportions of molecules, thetransform needs to be inverted. Inverting Laplace transformation ismathematically ill-posed, however (in contrast to Fouriertransformation) and the weighing factor therefore is determined bynumerical inverse Laplace transformation. In certain embodiments, sincethe inverse Laplace transformation is ill-posed and is numerical, it istherefore not unique and for that reason two or more different numericalinverse Laplace transformation algorithms are used for control purposes,including UPEN (See Borgia G C, Brown R J S, Fantazzini P.,Uniform-penalty Inversion of Multiexponential Decay Data, 132 J.MAGNETIC RESONANCE, 65-77 (1998); Borgia G C, Brown R J S, FantazziniP., Uniform penalty Inversion of Multiexponential Decay Data IL DataSpacing, T2 Data, Systematic Data Errors, and Diagnostic, 147 J.MAGNETIC RESONANCE, 273-85 (2000)), and RILT (see Regularized InverseLaplace Transform function available for Matlab Central) (all of whichare incorporated herein by reference in their entirety). The result ofthe inverse Laplace transformation can also be expressed as:

In(T₂) = ∫_(T₂min )^(T₂max )A(T₂)dT₂

where the integral In(T₂) is normalized to 100% at the maximum detectedT₂ value. FIG. 2 provides the result of the inverse Laplacetransformation of the embodiment data from FIG. 1, wherein curve 20provides the representation of the weighing factor A(T₂) and curve 22the representation of In(T₂). The internal plateau 24 visible in curve22 separates the in-pore and out-of-pore oil components. The in-pore oilis responsible for the initial upward slope 26 of curve 22 in the rangeof approximately 10 milliseconds or less. Thus, the fraction of in-porematerial is estimated by the plateau height 24 on the relative unitsscale of the y axis.

Use of various embodiments of this method can allow a skilled artisan todiscern several physico-chemical properties of a sample. In certainembodiments, a sample comprising a porous material and a liquid that isat least partially contained in the porous material is placed in aspectrometer, a pulse or pulse sequence is applied, the transverserelaxation decay is measured, and an inverse Laplace transformation isperformed. By examining the data as described above, the amount ofin-pore liquid and out-of-pore liquid can be determined. In certainembodiments, this establishes the capacity of a particular poroussubstance for a particular liquid, the efficiency of a pore loadingprocesses, or both. For example, in certain embodiments the efficiencyof filling pores via capillary action is determined.

In certain other embodiments, the sample may further comprise acontacting solution and the porous material and liquid are exposed tothe contacting solution. In some embodiments, this exposure is beforeany application of a RF pulse or pulse sequence and subsequentmeasurement, while in others one or more RF pulses or pulse sequencesare applied and subsequent measurements are taken before the exposure tothe solution. Various embodiments include any order of these steps. Insome embodiments, the initial state or states of a sample is clearlyascertained and its exposure to the contacting solution is then measuredand compared to the initial state or states. In other embodiments, onlythe state or states of the sample after exposure to the contactingsolution are measured. In embodiments where multiple pulses or pulsesequences are applied in a relatively short time period and multiplemeasurements are taken, such as in kinetic experiments, a predeterminedtime period separates the transverse relaxation decay measurements toensure the magnetization of the sample completely returns to itsoriginal strength along the z-axis. As is known in the art, the optimalamount of time should be determined experimentally for each sample.Certain embodiments of the method use two second delay betweentransverse relaxation decay measurements.

In certain other aspects of the invention, the long term steady state orlong term kinetics of the sample are measured. In some of theseembodiments, an initial transverse relaxation decay is measured beforethe porous material and liquid are exposed to the contacting solutionand one or more subsequent transverse relaxations are measured after theexposure. In certain embodiments, the one or more subsequent transverserelaxation decay measurements are taken minutes after exposure to thecontacting solution, in others hours later, and in still others dayslater. In yet other embodiments, the measurements are repeated onregular intervals of these time periods (e.g. approximately every 30minutes). The number of repeated measurement may be whatever number isneeded to acquire a sufficiently clear transverse relaxation decaydepending on the nuclear species of interest and subject to any desiredkinetic intervals. In some embodiments, 1, 2, 4, 8 or 16 transverserelaxations are measured. In others, at least 32, 64, 128, 256, or 512are measured to determine the amount of in-pore and out-of-pore oil.

In some embodiments, at least one subsequent transverse relaxation decayis measured after approximately 15 minutes, 1 hour, 6 hours, 12 hours,24 hours, 48 hours, or a combination thereof. In these embodiments,performing an inverse Laplace transformation on the initial and at leastone subsequent transverse relaxations and comparing the results providesthe long term steady state characteristics and/or long term kinetics ofthe sample. Among other benefits, a skilled artisan can use theseembodiments to examine the delivery of a medicament or a pharmaceuticalcompound in the gastric environment or the blood stream.

Certain other aspects of the invention relate to providing a method formeasuring the release kinetics of a liquid from inside a porousmaterial. In some embodiments, the method comprises placing a sample ina nuclear magnetic resonance probe, where the sample comprises a porousmaterial a liquid that is at least partially contained or imbibed insidethe porous material, and a contacting solution, wherein the contactingsolution is separated from the porous material and the at leastpartially imbibed liquid. The porous material and liquid then areexposed to the contacting solution, a RF pulse or pulse sequence isapplied and a transverse relaxation decay is measured. As noted above,the exposure to the contacting solution may occur before or after thefirst RF pulse/pulse sequence and subsequent measurement. After waitinga predetermined time period, one or more subsequent pulse/pulsesequences are applied and relaxations measured. In some embodiments, themeasurements begin almost immediately after exposure of the porousmaterial and liquid to the solution and are repeated at relatively shortintervals. Conversion of the measurements by inverse Laplacetransformation therefore provides the short term kinetic data for therelease kinetics of the liquid from the porous material into thecontacting solution.

The measurement of the sample's transverse relaxation decay can beginalmost immediately after the exposure of the porous material and liquidto the contacting solution. In certain embodiments, some dead time isrequired due to any mechanical disturbances such as fast internalconvection in the sample caused by the exposure. In some embodiments,the dead time is less than about 100 milliseconds after the exposure isinitiated. In certain other embodiments, especially those where theliquid is released relatively quickly, effective measurements can onlybegin approximately 500 milliseconds later as rapid convective flow ofthe liquid obliterates the signal at shorter times. As discussed above,some delay period between measurements is required for accurate results.In certain embodiments of the method, a two second delay is used, whichfor some samples allows accurate measurements of strong signal byallowing the magnetization to fully resume its initial state, yet isfrequent enough to provide insightful kinetic data. In other embodimentsand systems, however, any delay that provides accurate results and someinsight into the short term kinetics of the system may be used,including delays of approximately 0.5, 1, 1.5, 2.5, 3, 5, 10, 30, 60,120, or 180 seconds.

Any desired number of transverse relaxation decays may be measured. Insome embodiments, 512 relaxation measurements are taken to accuratelycapture the relevant kinetic period, while other embodiments useapproximately 8, 16, 32, 64, 128, 256, 612, 1024, or 2048 measurements.The appropriate number is in part dependent on the properties of theparticular sample and/or the desired applications of the sample.Similarly, the recording time for each transverse relaxation decay canvary across different embodiments. In some embodiments, the relaxationis recorded over approximately 500 milliseconds, while in others therecording time is approximately 100, 175, 250 or 750 milliseconds. Instill others the recording time is approximately 1 second, 1.25, 1.5,1.75 or 2 seconds.

In FIG. 3, plot 30 reflects the transverse relaxation data after theinverse Laplace transformation for an exemplary embodiment of therelease kinetics determination method. In this exemplary embodiment,porous SCTAB particles were loaded with medium chain triglyceride oiland exposed to a mucin buffer contacting solution. In FIG. 3, curve 31reflects the initial state of the sample before the porous material andoil were exposed to the buffer. As before the approximate plateau heightof the curve provides the relative proportions of in-pore and out ofpore-material, where here approximately 70% of the oil is inside thepores of the SCTAB. Curve 32 reflects the transverse relaxationmeasurement taken 500 milliseconds after exposure to the buffersolution, where approximately 50% of the oil remains inside the pores ofthe SCTAB material. Curve 33 reflects the transverse relaxationmeasurement taken 2 seconds later, or 2.5 seconds after exposure, andcurves 34-38 reflect representative measurements taken 8.5, 22.5, 42.5,100.5 and 354.5 seconds after exposure, respectively.

FIG. 4 provides the kinetic plot 40 for this exemplary embodiment, whereeach data point corresponds to the plateau height from FIG. 3 at theappropriate measurement time For example, point 41 reflects the plateauheight of curve 31 and shows the relative amount of the oil contained inthe pores of the SCTAB material. This technique therefore provides amanner for plotting the short term kinetics of liquid release from aporous material. This can have many beneficial applications. In onerepresentative example, one may probe and evaluate the delivery ofvarious flavorants in the mouth upon consumption of certain foods.

In some embodiments of the method, the measurement of the sample'stransverse relaxation begins almost immediately after the exposure ofthe porous material and the at least partially imbibed liquid to thecontacting solution. Traditional sample loading into an NMRspectrometer, however, often takes at least 10 seconds if notsignificantly longer depending on the characteristics of the machine andits operating program. Therefore, information about the initial stagesof a chemical reaction or other physico-chemical transformation oroperation, including the immediate short-term kinetics, cannot bemeasured using NMR when traditional sample loading is used since thereis an inherent delay before measurement after introducing the samplecomponents into cavity of the NMR tube. Thus, in certain embodiments,the porous material and liquid are exposed to the contacting solution insitu inside the NMR probe after the sample is loaded into the NMRspectrometer and the NMR probe is ready to measure the sample'stransverse relaxation.

In some embodiments, the porous material and liquid are stored in afirst container and the contacting solution is stored in a secondcontainer. In certain embodiments, the first and second containers arecylindrical, rectangular, or any other geometric shape. The porousmaterial and liquid are separated from the contacting solution beforebeing exposed to or coming into contact with the contacting solution. Insome embodiments, the first and second container share a wall thatseparates the porous material and liquid from the contacting solution.In certain embodiments, the probe may include moveable structure topermit or initiate exposure between the substances in the first andsecond containers, such as by moving structure from a first position toa second position. For example, in one embodiment, the wall is lifted upfrom the sample area to expose the sample components to each other. Asanother example, in another embodiment, the wall comprises one or moreslits or openings that can selectively open up to cause exposure. Incertain other embodiments, the first and second container are spatiallyseparated, and exposure may be accomplished by moving one or more of thesubstances within the probe. In one example embodiment, the porousmaterial and liquid may be injected into the second container, and inanother example embodiment, the contacting solution is injected into thefirst container. In some embodiments, the sample container positionedinside the NMR probe comprises the first container, the secondcontainer, or both. In certain exemplary embodiments, the samplecontainer is configured to hold the sample components so that, onceloaded into a NMR spectrometer, the sample components are alreadypositioned inside the sample space, i.e. within the probe coil, the areawhere the generated magnetic field is at its maximum strength, or both.These embodiments advantageously eliminate any relaxation effects orspin polarization artifacts that result from moving sample componentsfrom an area experiencing a lower magnetic field strength to the samplespace experiencing a relatively higher magnetic field strength as movingeven centimeters from the sample space results in a noticeabledifference in magnetic field strength. In certain embodiments, at leastthe portion of the sample container that is positioned inside the NMRprobe is cylindrical. In some embodiments the cylinder is approximately3 mm, 5 mm, 8 mm, 10 mm or 15 mm in diameter. In various embodiments,the cylinder is a standard NMR measurement tube.

In some embodiments, the first container is contained inside the secondcontainer, and exposure may be accomplished in a number of differentways. For example, in one embodiment, the first container is thenremoved to create exposure, in another embodiment, the material isforced outside of the first container into the second container, and ina further embodiment, a combination of such techniques may be used.Further structures and techniques may be used in additional embodiments.These actions may be driven by a wide variety of mechanical components,including but not limited to a piston, a shaft, a holder, or acombination thereof. In some embodiments these components are capable ofmoving up or down the longitudinal axis of the probe. In someembodiments, the removal or forcing is powered by mechanical power,hydraulic power, pneumatic power, electrical power, human power, or acombination thereof.

In certain embodiments, the exposure is achieved by an exposuremechanism using an actuator that is operably connected to one or moremoveable elements. This connection may be direct or indirect, and themoveable elements may be any suitable mechanical component such as thosedescribed above. In some embodiments, the actuator moves the one or moremoveable elements between a first position and one or more subsequentpositions. In certain embodiments, the movement of the moveable part orparts to the second position may permit or initiate the exposure ofvarious sample components such as the porous material, liquid and thecontacting solution, such as by removing any separating barriers,driving the components together, driving one or more components intoanother, or a combination thereof. In some embodiments, when themoveable element or elements are in second position the porous materialand liquid are exposed to the contacting solution, the porous materialand liquid are driven into the contacting solution, or both. Theactuator can be any type known in the art, including but not limited toa lever arm and cable, a screw, a nut, a chain, a rod, a linkage, alinear cam, a rotatable cam, an active material such as a piezoelectric,an electric, pneumatic, or hydraulic actuator, and the like.

In some embodiments, an electric current is applied to a conductormaterial such that, in the applied magnetic field of the NMRspectrometer, the electric current flowing through the conductormaterial results in a Lorentz Force acting upon the conductor material.In turn, this force may be used to mechanically move one or morestructures within the probe to result in exposure of the porous materialand liquid with the contacting solution. This force can be defined bythe equation:

F=Il×B

where I is the current flowing though the conductor material, l is thelength of the conductor material and B is the magnetic field. In certainembodiments, the conductor material is an un-curved wire or is otherwisestraight or shaped so that the electric current substantially moves in asingle direction and is positioned so that the flow of current I isperpendicular to the direction of the applied magnetic field. Underthese conditions, the conductor material will experience a force pushingin a perpendicular direction according to the right hand rule when anelectric current is flowing. In some embodiments, the conductor materialis shaped and oriented in this way so that, when the electric current isapplied, it moves in a particular direction. This movement can be usedto achieve exposure of the porous material and liquid with thecontacting solution, such as by moving barriers between the substances,forcibly moving one or more of the substances, or a combination thereof.In various example embodiments, the movement of the conductor materialmay be transferred to initiate or perform the removing of the first orsecond container, the forcible movement of the porous material and theliquid, the forcible movement of the contacting solution, or acombination thereof. The movement from the Lorentz force can directly orindirectly move various other components including the first container,the second container, the piston, the shaft, a wall separating the firstand second containers, or a combination thereof. In one embodiment, theprobe may include a moveable actuator connected to the conductormaterial and operably connected to one or more other components of theprobe. The movement of the conductor material may create movement of theactuator, which in turn can move the other component(s) of the probe inthe process of creating exposure.

In certain embodiments, the conductor material is a coiled wire or asolenoid coil. When an electric current is applied to the coil the forceis defined by the equation:

F=I∫dl×B.

where the variables are defined as before. In these embodiments, thesolenoid coil will experience torque when the electric current isapplied. In certain embodiments, a solenoid coil is used such that theapplication of the electric current causes a Lorentzian torque thatdrives rotation of the coil, and this initiates or performs movement ofone or more components of the probe, such as the removal and/or forcingsteps described above.

FIG. 5 illustrates an exemplary embodiment of an in situ reaction probestructure 50, where 50 a denotes the structure in a first positionbefore initiating exposure to the contacting solution and 50 b denotesthe structure in a second position after initiating exposure. The probestructure 50 includes an exposure mechanism 63 that can expose at leasta first sample component to at least a second sample component inside asample container within the probe 50. In this exemplary embodiment, theprobe 50 includes a first sample component in the form of the porousmaterial and the least partially imbibed liquid 51 inside a firstcontainer 52, where in this exemplary embodiment the first container 52is a first cylindrical tube with a cylindrical wall 85. The wall 85 ofthe first container 52 functions as a separator to separate the porousmaterial and liquid 51 from a second sample component in the form of thecontacting solution 53 in a second container 54, where the secondcontainer 54 is a second cylindrical tube that surrounds the firstcylindrical tube. In this embodiment, therefore, the second container 54contains all the sample components and the first container 52 therein.In this exemplary embodiment, the first tube is hermetically sealed fromthe contents of the second tube, which may be accomplished by using aseal, plug, gasket, or another sealing means or component.

In this exemplary embodiment, the exposure mechanism 63 includes amovable actuator 55 that comprises the conductor material in the form ofa solenoid coil and is connected to one or more other moveablecomponents of the exposure mechanism 63, such that movement of theactuator 55 moves one or more other components from a first position toa second position. This movement initiates the exposure. The actuator 55in this embodiment has a first member 64 coupled to a moveable piston 56connected to a shaft 57 that is in communication with the firstcontainer 52, and a second member 65 that is coupled to a moveableholder 58 that is connected to the wall of the first container 52. Asillustrated in FIG. 5, the first and second members 64, 65 may be armsextending from opposite sides of the actuator 55, which are connected tothe shaft 57 and the holder 58, respectively, by connectors 66. In thisembodiment, the actuator 55 is rotatable or pivotable about an axis ofrotation 67, and the first and second members 64, 65 extend generally inopposite directions from the axis 67. It is understood that the solenoidcoil or other conductor material may form the entirety or substantialentirety of the actuator 55 in another embodiment.

In the embodiment illustrated in FIG. 5, an electric current is appliedto the solenoid coil, causing it to rotate in the clockwise direction,which causes rotational movement of the actuator 55 (from position 55 ato 55 b). This rotation causes the first member 64 to move downward,which drives the piston 56 to push the shaft 57 axially down into theporous material and the liquid 51, forcing the porous material and theliquid 51 downward. This rotation also simultaneously causes the secondmember 65 to move upward, which pulls the holder 58 upward, raising thefirst container 52 and removing the separator between the components 51and 53. This action results in the creation of a mixture 59 of theporous material, liquid and contacting solution, which can then beprobed with the NMR spectrometer. In this embodiment, the mixture 59 ispositioned in the second container 54 after exposure, and the secondcontainer thereby also forms the sample container for holding themixture 59 for probing.

In certain embodiments, the components that do not come in contact withthe sample and do not come into close proximity of the sample, which caninclude at least the actuator, solenoid, piston, shaft, or holderdepending on the characteristics of the embodiments, are made from apolymer such as caprolon or a metal material such as brass, copper,steel, bronze, or tin. In various embodiments, the components that docome in contact with the sample or come into close proximity of thesample are made of materials that are either substantially or completelyfree of Hydrogen or other nuclear species that may be probed by NMR orexhibit very short transverse relaxation times so that they do notinterfere with the transverse relaxation decays of the liquid ofinterest. In certain embodiments, “close proximity” is determined asbeing close enough to overlap with or interfere with the magnetic fieldgenerated by the NMR probe coil during pulse sequences or signalmeasurements. In some embodiments, these components are made ofmaterials that have chemical resistance to one or more commonly usedsolvents. In certain embodiments, these components are made of glass,quartz glass, Teflon, or a combination thereof. In various embodiments,some or all of these components are a permanent part of the NMR probeand are moveable to allow sample loading, while in others some or all ofthe components comprise a removeable probe insert.

In accordance with yet another aspect of the invention, a method forperforming chemical reactions or other physico-chemical operationsbetween two or more components in situ inside a nuclear magneticresonance probe is provided. In some embodiments, the method comprisesloading a sample into a sample container, where a separator separates atleast a first sample component of the sample from at least a secondcomponent of the sample, placing the sample in a spectrometer, andexposing at least the first sample component to at least the secondsample components when the sample is ready for the application of one ormore RF pulses or pulse sequences. The wall of the first container 52 inFIG. 5 is one example of such a separator, and other examples aredescribed herein. It is understood that the separator may be formed byfurther structures that are not described herein and function toseparate the components. In certain embodiments, the separator separatesthree or more sample components from each other before exposure. Afterthe exposure, any type of NMR measurement and analysis may be performed.In certain embodiments, the data acquisition is focused solely onstandard spectra and chemical shift data. Other embodiments relate toother known NMR experiments, including but not limited to APT, INEPT,DEPT, NOE, COSY, NOESY, HETCOR, HMQC, HMBC, HETJ, RELAY, DQFCOSY,TQCOSY, TOCSY, INADEQUATE, HOMJ, ROESY, PFG, gCOSY, gDQFCOSY, gHECTOR,gHMQC, or gHMBC. In certain embodiments, the NMR data is analyzed usinga Fourier transform or a inverse Laplace transform. In some embodiments,both the first and second sample component are liquids, while in othersat least one comprises a solid or a gas.

In certain embodiments, at least the first sample component is exposedto at least the second sample component by lifting a separator fromdividing the sample, forcing at least the first sample component intocontact with the second sample component, or a combination thereof. Insome embodiments this is done by an exposure mechanism, which maycomprise an actuator, one or more moveable parts that are configured tomove between a first and at least a second position when driven by theactuator. In still other embodiments, the method further comprisesapplying an electric current to a conductor material such that theconductor material moves or rotates in a particular way due to a Lorentzforce. In yet other embodiments, the conductor material is a solenoidcoil and the electric current produces a Lorentzian torque that causesthe solenoid coil to rotate. In some embodiments, the rotation of thesolenoid coil directly or indirectly lifts up the separator whilemechanically forcing at least the first sample component into contactwith at least the second sample component.

In certain embodiments, the separator is a tube having a first diameterand the sample container is a tube having a second diameter, the seconddiameter being larger than and concentric with the first diameter. Instill other embodiments, the first sample component is forced intocontact with at least the second sample component using a shaft movingalong a longitudinal axis of the sample container.

These method descriptions are merely exemplary. In certain embodiments,the methods may include additional combinations or substitutions of someor all of the steps described above. Moreover, all aspects, structures,features or components of any of apparatuses of the invention mayperform or be included in any appropriate step of the methods. Finally,additional and alternative suitable variations, forms and components forthese methods will be recognized by those skilled in the art given thebenefit of this disclosure.

Other aspects of the invention relate to apparatuses for performing theinventive methods. In some embodiments, these apparatuses comprise oneor more of the structures, features components or combination thereofdiscussed above in relation to the methods of the invention. Variousembodiments combine software and hardware aspects. In some embodiments,these aspects take the form of a computer program product stored by oneor more non-transitory computer-readable storage media havingcomputer-readable program code, or instructions, embodied in or on thestorage media. The term “computer-readable medium” or “computer-readablestorage medium” as used herein includes not only a single medium orsingle type of medium, but also a combination of one or more mediaand/or types of media. Such a non-transitory computer-readable mediummay store computer-readable instructions (e.g., software) and/orcomputer-readable data (i.e., information that may or may not beexecutable). Any suitable computer readable media may be utilized,including various types of tangible and/or non-transitory computerreadable storage media such as hard disks, CD-ROMs, optical storagedevices, magnetic storage devices, and/or any combination thereof.

In certain embodiments, the apparatuses further comprise one or morenon-transitory computer readable media storing computer readableinstructions that, when executed by a computer processor, cause theapparatus to perform any of the method steps described above, includingbut not limited to exposing a porous material and a liquid to acontacting solution, applying an electrical current to a conductormaterial, applying one or more radiofrequency pulses or pulse sequences,measuring one or more transverse relaxations of the sample, performingan inverse Laplace transformation using the computer processor on thetransverse relaxations to determine amount of the liquid containedinside the porous material and an amount of the liquid outside theporous material, waiting a predetermined time period between pulses orpulse sequences, comparing or plotting various amounts of in-pore andout-of-pore liquid, activating an exposure mechanism, activating anactuator, lifting a separator, forcing a sample component, removing acontainer, or a combination thereof.

As noted above, some aspects of the embodiments disclosed herein may beexecuted by one or more processors on a computing device. Suchprocessors may execute computer-executable instructions stored onnon-transitory computer-readable media. FIG. 12 illustrates a blockdiagram of a generic computing device 120 that may be used according toan illustrative embodiment of the disclosure. The computing device 120may have a processor 121 for controlling overall operation of the deviceand its associated components, including RAM 122, ROM 123, input/outputmodule 124, and memory 125. Input/Output (I/O) 124 may include amicrophone, keypad, touch screen, camera, and/or stylus through which auser of computing device 120 may provide input, and may also include oneor more of a speaker for providing audio output and a video displaydevice for providing textual, audiovisual and/or graphical output. OtherI/O devices through which a user and/or other device may provide inputto the computing device 120 also may be included.

Software may be stored within memory 125 and/or storage to provideinstructions to processor 121 for enabling computing device 120 toperform various functions. For example, memory 125 may store softwareused by the computing device 120, such as an operating system 126,application programs 127, and an associated database 128. The computingdevice 120 is connected to the NMR Spectrometer 130 through aspectrometer interface 129. In some embodiments the application programs127 may include NMR operation programs or data interpretation programscapable of analyzing the measured NMR signals, including programscapable of performing Fourier transformations, Laplace transformations,or inverse Laplace transformations. FIG. 13 provides a simplified blockdiagram of an exemplary embodiment of a computer operated NMRmeasurement apparatus 130 (please note the portions of the figure notshown in block form are illustrative only and are explicitly not drawnto scale). In this embodiment, the computing device 120 is connected viathe spectrometer interface 129 (not shown) to various components of theNMR spectrometer 135, including the RF transmitter 131, the RF receiver133, and the electrical source 134, where the NMR spectrometer comprisesa probe coil 132 and a magnet 136. The computer operated NMR measurementapparatus 130 may include other standard components, including but notlimited to sample changers, lock transmitters, lock receiver,temperature regulation, amplifiers, shim regulation components orgradient control/amplifier components. In some embodiments, the NMRmagnet has a field strength of approximately 11.7 Tesla, while in othersit ranges from approximately 1.41 Tesla to approximately 23.5 Tesla. Incertain embodiments, the NMR magnet has a field strength ofapproximately 2.35 Tesla, 4.7 Tesla, 7.05 Tesla, 14.1 Tesla, 18.8 Tesla,21.1 Tesla, or 23.5 Tesla.

In this exemplary embodiment, when the computer processor 121 (notshown) executes certain computer-executable instructions stored onnon-transitory computer-readable media, the computing device 120 causesthe RF transmitter 131 to send a RF pulse or pulse sequence to thesample via the probe coil 132, and then the RF receiver 133 measures thereceived NMR signals from the probe coil 132. In this exemplaryembodiment, the computing device 120 also causes the electrical source134 to send an electrical current though the solenoid coil 137, wherethis may occur before or after the RF pulse or pulse sequence is appliedto the sample. In other embodiments, the computing device 120 isdirectly or indirectly connected to another type of actuator asdescribed above. In certain other embodiments, no actuator, solenoidcoil or the like components for performing in situ reactions arepresent.

These descriptions of the apparatuses are merely exemplary. In certainembodiments, the apparatuses comprise additional combinations orsubstitutions of some or all of the components described above inrelation to any of the disclosed methods or apparatuses. Moreover,additional and alternative suitable variations, forms and components forthe apparatuses will be recognized by those skilled in the art given thebenefit of this disclosure.

All of the above described method and apparatus descriptions for variousaspects of the invention are representative. In certain embodiments, amethod or apparatus may include additional combinations or substitutionsof some or all of the steps and/or components described herein or theirequivalents. Moreover, additional and alternative suitable variations,forms and components will be recognized by those skilled in the artgiven the benefit of this disclosure.

EXAMPLES

The above inventive methods and apparatuses were investigated by aseries of exemplary experiments. All of the representative experimentsdiscussed herein were performed by a ¹H NMR in a Bruker Avance 500 NMRspectrometer with a resonance frequency of 500.13 MHz. A CPMG pulsesequence was applied in each of these experiments. As noted above CPMGexperiments can be performed with different pulse spacing times. Thepulse spacing values used were the below noted values where there was nosignificant prolongation of the signal decays. This was tested byrecording transverse relaxation decays with different pulse spacing inthe CPMG sequence for every sample. The comparison of those decaysprovided an indication of the threshold pulse spacing value below whichthere were no significant artifacts.

Example 1

Two samples of SP104 powder were loaded (imbibed) with an equivalentamount of medium chain triglyceride oil. In one sample, an additional 3mg of the oil was then added to the sample. FIG. 6 provides the plot 60of the measurement of the transverse relaxation distribution of eachsample after performance of the inverse Laplace transformation. Curve 61shows the data for the sample with the additional oil added and curve 62shows the data for the sample without the additional oil. The portion ofthe curves below the plateau signifying the amount of in-pore oil areequivalent, while the signal for out-of-pore oil is much larger forcurve 61 illustrating the sample with additional oil added. This clearlyshows the portion of the curve after the plateau reflects the relativeamount of out-of-pore material that exhibits a longer transverserelaxation time.

Example 2

One sample of P104 powder was filled with medium chain triglyceride oil.A second was filled with heavy water and then 5 mg of the same oil wassubsequently added. FIG. 7 provides the plot 70 of the measurement ofthe transverse relaxation distribution of each sample after performanceof the inverse Laplace transformation. Curve 71 shows the data for thesample with just the oil and curve 72 shows the data for the sampleinitially loaded with heavy water. The portion of curve 72 before theplateau is minimal, clearly showing the portion of the curve before theplateau reflects in-pore material with a shorter transverse relaxationtime.

Example 3—Long Term Steady State

Twenty samples were prepared to examine the long term steady statereached 24 hours after a liquid and porous material combination wereadded into an aqueous contacting solution. These tests were performedwith a DIFF30 diffusion probe equipped with a 5 mm ¹H radiofrequencyinsert. A 7.5 microsecond length 90 degree pulse was used. Allspectrometer shims were set to zero and the magnetic field wascalibrated to zero frequency offset. Samples of porous powders with aweight of 30-40 mg were placed in a 5 mm NMR tube. Several transverserelaxation curves were recorded to improve the signal to noise ratio.Table 1 illustrates the results comparing the initial and 24 hours ofin-pore and out-of-pore ratios. After twenty four hours, all in-porematerial has settled to the bottom of the sample as sediment, and thefraction of oil released into the solution from the buffer was at thetop of the sample. Data for the following samples was taken:

-   -   Sample 1: SP104 porous material was loaded with medium chain        triglyceride oil (“MCT”) and released into a mucin buffer;    -   Sample 2: SP104 porous material was loaded with MCT and released        into an electrolyte buffer without mucin;    -   Sample 3: SP104 porous material was loaded with sunflower oil        (“SF”) and released into a mucin buffer;    -   Sample 4: SP104 porous material was loaded with SF and released        into an electrolyte buffer without mucin;    -   Sample 5: SP104 porous material was loaded with propylene glycol        (“PG”) and released into a mucin buffer;    -   Sample 6: SP104 porous material was loaded with PG and released        into an electrolyte buffer without mucin;    -   Sample 7: SP104 porous material was loaded with glycerine and        released into a mucin buffer;    -   Sample 8: SP104 porous material was loaded with glycerine and        released into an electrolyte buffer without mucin;    -   Sample 9: SCTAB porous material was loaded with MCT and released        into a mucin buffer;    -   Sample 10: SCTAB porous material was loaded with MCT and        released into an electrolyte buffer without mucin;    -   Sample 11: SCTAB porous material was loaded with SF and released        into a mucin buffer;    -   Sample 12: SCTAB porous material was loaded with SF and released        into an electrolyte buffer without mucin;    -   Sample 13: SCTAB porous material was loaded with PG and released        into a mucin buffer;    -   Sample 14: SCTAB porous material was loaded with PG and released        into an electrolyte buffer without mucin;    -   Sample 15: SCTAB porous material was loaded with glycerine and        released into a mucin buffer;    -   Sample 16: SCTAB porous material was loaded with glycerine and        released into an electrolyte buffer without mucin;    -   Sample 17: SP104 porous material was loaded with MCT and meat        flavor, and then released into a mucin buffer;    -   Sample 18: SP104 porous material was loaded with MCT and meat        flavor, and then released into an electrolyte buffer without        mucin;    -   Sample 19: SP104 porous material was loaded with PG and meat        flavor, and then released into a mucin buffer; and    -   Sample 20: SP104 porous material was loaded with PG and meat        flavor, and then released into an electrolyte buffer without        mucin.

TABLE 1 Fraction of in-pore Oil Fraction of out-of-pore Oil Fraction (%± 0.5%) (% ± 0.5%) of Oil After After Release Released Sample InitialRelease in Initial in Solution to Solution No. State Solution State (insediment) [%] 1 62.0 52.0 38.0 12.0 36.0 2 62.0 52.5 38.0 12.5 35.0 368.0 14.0 32.0 52.0 34.0 4 68.0 14.5 32.0 60.5 25.0 5 74.0 63.5 26.024.5 12.0 6 74.0 65.0 26.0 35.0 0.0 7 65.0 31.0 35.0 58.0 11.0 8 65.032.0 35.0 57.0 11.0 9 61.5 52.5 38.5 10.5 37.0 10 61.5 51.5 38.5 31.517.0 11 69.0 3.0 31.0 17.0 80.0 12 69.0 7.5 31.0 12.5 80.0 13 55.0 1.545.0 11.5 87.0 14 55.0 2.0 45.0 7.0 91.0 15 74.5 1.5 25.5 11.5 87.0 1674.5 1.5 25.5 9.5 89.0 17 80.0 1.0 20.0 16.0 83.0 18 80.0 1.5 20.0 14.584.0 19 76.0 4.5 24.0 13.0 82.5 20 76.0 6.0 24.0 14.0 80.0

For the samples with glycerine or propylene glycol, these liquidssolubilized in the buffer solutions. Thus, almost all the liquid isreleased from the pores and goes into the aqueous phase—any remainingliquid in the pores after 24 hours is the faction that is dissolved inthe solution filling the pores.

Example 4—Release Kinetics

Ten samples were prepared to examine the release kinetics of a liquidfrom a porous material once added into an aqueous contacting solution.These tests were performed at 500 MHz ¹H frequency with a DIFF30diffusion probe equipped with 10 mm ¹H radiofrequency inserts. A 11.5microsecond length 90 degree pulse was used. All spectrometer shims wereset to zero and the magnetic field was calibrated to zero frequencyoffset. Liquid loaded powders with a weight of 58-63 mg were placed intoan inner tube (similar to tube 52 in FIG. 5) and the space between theinner tube and outer tube (similar to tube 54 in FIG. 5) was filled with0.3 mL of a contacting solution. The pulse delays of the CPMG experimentwere set based on the results of the corresponding long term steadystate experiments. Several transverse relaxation curves were recorded toimprove the signal to noise ratio. Data for the following samples wastaken:

-   -   Sample 1: SP104 porous material was loaded with MCT and released        into a mucin buffer, where the CPMG sequence utilized a 155        microsecond pulse delay;    -   Sample 2: SP104 porous material was loaded with SF and released        into a mucin buffer, where the CPMG sequence utilized a 155        microsecond pulse delay;    -   Sample 3: SP104 porous material was loaded with PG and released        into a mucin buffer, where the CPMG sequence utilized a 155        microsecond pulse delay; and    -   Sample 4: SP104 porous material was loaded with Glycerine and        released into a mucin buffer, where the CPMG sequence utilized a        155 microsecond pulse delay.

The kinetic plots from samples 1-4 are provided in FIG. 8, where plot 81shows the kinetic data for sample 1, 82 the plot for sample 2, 83 forsample 3, and 84 for sample 4.

-   -   Sample 5: SCTAB porous material was loaded with MCT and released        into a mucin buffer, where the CPMG sequence utilized a 55        microsecond pulse delay;    -   Sample 6: SCTAB porous material was loaded with SF and released        into a mucin buffer, where the CPMG sequence utilized a 55        microsecond pulse delay;    -   Sample 7: SCTAB porous material was loaded with PG and released        into a mucin buffer, where the CPMG sequence utilized a 55        microsecond pulse delay; and    -   Sample 8: SCTAB porous material was loaded with Glycerine and        released into a mucin buffer, where the CPMG sequence utilized a        55 microsecond pulse delay.

The kinetic plots from samples 5-8 are provided in FIG. 9, where plot 95shows the kinetic data for sample 5, 96 the plot for sample 6, 97 forsample 7, and 98 for sample 8.

-   -   Sample 9: SP104 porous material was loaded with SF and released        into a Deuterated Chloroform buffer, where the CPMG sequence        utilized a 255 microsecond pulse delay.    -   Sample 10: Re-dried powder from sample 9 released into an        electrolyte buffer without mucin buffer, where the CPMG utilized        a 255 microsecond pulse delay.    -   The kinetic plots from samples 9 and 10 are provided in FIG. 10,        where plot 109 shows the kinetic data for sample 9, and plot 110        shows the data for sample 10.

When comparing the plots in FIG. 10 it is important to recall the amountof SF oil is constant. When the solvent was evaporated most of the oil(over 90%) resided in-pore compared to a much smaller number (just over50%) previously, where presumably some of this oil was stuck on theoutside surface of the powder. This type of experiment can be used todetermining the filling capabilities of a certain systems and/ormaterial by capillary action.

All kinetic curves were fitted using a Levenberg-Marquardt least-squaresfitting algorithm to a model of the same of two exponential functionwith five unlocked fitting parameters. The parameters were:

-   -   I₀—initial amplitude, the percentage of in-pore oil in the        initial state. Approximate error is ±2%;    -   P—relative proportion of the faster of the two transverse        decays. The proportion of the slower decay is 1−P;    -   I_(long)—the long-time baseline, the percentage of in-pore oil        in the long-time (˜1000 second) limit (note this parameter is        not the same as that obtained after 24 hours and presented in        Table 1). Approximate error is ±2%;    -   τ_(fast) and τ_(slow)—the two time constants.

TABLE 2 Initial Amount of Release Time Relative Sample in-pore Oil OilRemaining τ_(fast) τ_(slow) for Half of the Proportion of No. I_(o [%])in-pro I_(long [%]) [s] [s] in-pore Oil [s] the fast decay P 1 61 51 2.4 34* 2.3 0.69 2 73 63 6 84 6 0.73 3 69 4.5 0.14 16 0.13 0.80 4 75 1 0.1423 0.11 0.88 5 68 20 0.5 78 0.9 0.57 6 65 33 0.12* 95 0.2* 0.61 7 55 10.06  80* 0.04 0.95 8 80 0 0.05 67 0.04 0.92 9 50 12 3.5 103  13 0.47 1088 58 3 85 5 0.56 *parameters with large inaccuracy.

Comparing the fitted curves and/or the raw kinetic data allowscomparison of the release behavior and kinetics of different materials.As a representative example, FIG. 11 provides a plot 113 where the twocurves 111 and 115 show the fitted curve for the kinetic data of samples1 and 5, respectively, clearly illustrating the difference in releasekinetics and the faster delivery of MCT from the SCTAB porous materialcompared to SP104, despite having an initially higher amount of in-poreMCT (68% in-pore initially for SCTAB compared to 61% in-pore for theSP104 material).

What is claimed is:
 1. An apparatus for performing chemical reactions insitu inside a nuclear magnetic resonance probe, the apparatuscomprising: a sample container; a separator that separates at least afirst sample component of a sample from at least a second samplecomponent of the sample inside the sample container; and an exposuremechanism comprising an actuator operably connected to at least a firstmoveable element, wherein the actuator is configured to move the firstmoveable element between at least a first position and a secondposition, and wherein the first sample component is separated from thesecond sample component when the first moveable element is in the firstposition and the first sample component is exposed to the second samplecomponent inside the sample container when the first moveable element isin the second position; wherein the exposure mechanism can beselectively activated to expose at least the first sample component toat least the second sample component inside the sample container at anytime after the components are loaded, including when the sample isloaded into a nuclear magnetic resonance spectrometer such that it isready for the application of a radiofrequency pulse or pulse sequence bya nuclear magnetic resonance probe; and wherein the sample components,when the sample container is loaded into the nuclear magnetic resonancespectrometer, are positioned within a sample space encircled by a probecoil of the nuclear magnetic resonance probe.
 2. The apparatus of claim1, wherein the actuator is operably connected to at least a secondmoveable element and the actuator is configured to move the secondmoveable element between at least a first position and a secondposition, and wherein the first sample component is separated from thesecond sample component when the second moveable element is in the firstposition and the first sample component is exposed to the second samplecomponent inside the sample container when the second moveable elementis in the second position.
 3. The apparatus of claim 1, wherein themoveable element comprises the separator, wherein the separatorseparates the first sample component and the second sample componentwhen the moveable element is in the first position, and wherein thefirst sample component is exposed to the second sample component whenthe moveable element is in the second position.
 4. The apparatus ofclaim 1, wherein the moveable element is configured to move the firstsample component to initiate exposure of the first sample component andthe second sample component when the moveable element moved from thefirst position to the second position.
 5. The apparatus of claim 1,wherein the exposure mechanism is configured to lift the separator fromthe sample, force the first sample component into contact with thesecond sample component, or a combination thereof when activated.
 6. Theapparatus of claim 5, the exposure mechanism further comprising anelectrical source and the actuator comprises a conductor materialelectrically connected to the electrical source, wherein the actuator ismounted such that it is configured to move or rotate in a particular waydue to a Lorentz force when an electrical current is supplied by theelectrical source to the conductor material and the conductor materialis in the presence of a magnetic field.
 7. The apparatus of claim 6,wherein the conductor material is a solenoid coil and the electriccurrent produces a Lorentzian torque that causes the solenoid coil torotate.
 8. The apparatus of claim 7, wherein the rotation of thesolenoid coil is configured to lift up the separator while mechanicallyforcing at least the first sample component into contact with at leastthe second sample component.
 9. The apparatus of claim 1, wherein theseparator is a tube having a first diameter, the sample container is atube having a second diameter, the second diameter being larger than thefirst diameter.
 10. The apparatus of claim 1, wherein the moveableelement comprises a shaft capable of moving at least the first samplecomponent along a longitudinal axis of the apparatus such that it isconfigured to drive the first sample component into contact with thesecond sample component when the moveable element moved from the firstposition to the second position.
 11. A method for performing chemicalreactions in situ inside a nuclear magnetic resonance probe, the methodcomprising: loading a sample into a sample container, wherein aseparator separates at least a first sample component of the sample fromat least a second sample component of the sample inside the samplecontainer; placing the sample into a nuclear magnetic resonancespectrometer, wherein the sample components, once the sample is placedinto the nuclear magnetic resonance spectrometer, are positioned withina sample space encircled by a probe coil of a nuclear magnetic resonanceprobe; exposing at least the first sample component to at least thesecond sample component inside the sample container when the sample isready for the application of a radiofrequency pulse or pulse sequence bythe nuclear magnetic resonance probe.
 12. The method of claim 11,wherein at least the first sample component is exposed to at least thesecond sample component by lifting the separator from the sample,forcing at least the first sample component into contact with the secondsample component, or a combination thereof.
 13. The method of claim 12,further comprising applying an electrical current to a conductormaterial such that the conductor material moves or rotates in aparticular way due to a Lorentz force.
 14. The method of claim 12,wherein the conductor material is a solenoid coil and the electriccurrent produces a Lorentzian torque that causes the solenoid coil torotate.
 15. The method of claim 14, wherein the rotation of the solenoidcoil lifts up the separator while mechanically forcing at least thefirst sample component into contact with at least the second samplecomponent.
 16. The method of claim 11, wherein the separator is a tubehaving a first diameter, the sample container is a tube having a seconddiameter, the second diameter being larger than the first diameter. 17.The method of claim 11, further comprising forcing at least the firstsample component into contact with at least the second sample componentusing a shaft moving along a longitudinal axis of the sample container.18. An apparatus for performing chemical reactions in situ inside anuclear magnetic resonance probe, the apparatus comprising: a samplecontainer; a separator that separates at least a first sample componentof a sample from at least a second sample component of the sample insidethe sample container, wherein at least one sample component comprises asolid material, and wherein the sample components, when the samplecontainer is loaded into a nuclear magnetic resonance spectrometer, arepositioned within a sample space encircled by a probe coil of thenuclear magnetic resonance probe; one or more non-transitory computerreadable media storing computer readable instructions that, whenexecuted by a computer processor, cause the apparatus to: activate anexposure mechanism to expose at least the first sample component to atleast the second sample component inside the sample container; apply afirst radiofrequency pulse or pulse sequence to the sample; and measurethe sample's magnetic resonance signals; wherein the exposure mechanismcomprises an actuator operably connected to at least a first moveableelement, wherein the actuator is configured to move the first moveableelement between at least a first position and a second position, andwherein the first sample component is separated from the second samplecomponent when the first moveable element is in the first position andthe first sample component is exposed to the second sample componentinside the sample container when the first moveable element is in thesecond position.
 19. The apparatus of claim 18, wherein the instructionsare configured to cause the exposure mechanism to lift a separator fromthe sample, force at least the first sample component into contact withthe second sample component, or a combination thereof when activated.20. The apparatus of claim 19, wherein the exposure mechanism furthercomprises an electrical source and a conductor material electricallyconnected to the electrical source, the conductor material is directlyor indirectly connected to the separator, and the conductor material ismounted such that it will move or rotate in a particular way due to aLorentz force when an electrical current is supplied by the electricalsource to the conductor material and the conductor material is in thepresence of a magnetic field.